Japan team first to make liver from stem cells

PARIS – Scientists in Japan said Wednesday they had grown human liver tissue from stem cells in a world first that holds promise for alleviating the critical shortage of donor organs.

Creating lab-grown tissue to replenish organs damaged by accident or disease is a holy grail for the pioneering field of research into the premature cells known as stem cells.

But Takanori Takebe of Yokohama City University’s graduate school of medicine and a team reported in the journal Nature that they grew tissue “resembling the (human) adult liver” in a lab mouse. They first created induced pluripotent stem (iPS) cells that they mixed with other cell types and coaxed them into “liver buds” — the precursor clusters that develop into a liver.

The buds, each measuring about 5 mm, were then transplanted onto a mouse brain, where they were observed transforming into a “functional human liver” complete with blood vessels, the scientists wrote.

“To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells,” said the report, adding the technique has yet to be tested on humans, but serves as an important proof of concept.

Stem cells are infant cells that can develop into any part of the body. Until a few years ago, when iPS cells were first tapped, the only way to get stem cells was to harvest them from human embryos.

This is controversial because it requires the destruction of the embryo, a process religious conservatives and others object to. But iPS cells are easily obtainable mature cells that are “reprogrammed” into a versatile, primitive state from where they can develop into any kind of cell in the body.

Takebe told a news conference ahead of the report’s release that the man-made liver was observed through a replacement glass skull that was fitted around the mouse’s brain.

The liver developed blood vessels that fused with those of the animal. It also performed certain human-specific liver functions — producing proteins and processing specific drugs.

“We have concluded that this liver is functioning,” the scientist said. “We think this is enough for improving the survival (rate) after liver failure.”

Other scientists described the research as promising.

“This opens up the distinct possibility of being able to create minilivers from the skin cells of a patient dying of liver failure,” Malcolm Alison, professor of stem-cell biology at London’s Queen Mary University, said in a statement issued by its science media center.

“Human mature liver cells transplanted on their own can fail to thrive,” he said, “but if immature liver cells are first combined with their normally nurturing supportive cells, they can mature in the transplanted host and function efficiently.”

Dusko Ilic from Kings College London said “the promise of an ‘off-shelf liver’ seems much closer than one could hope even a year ago,” although the technique has yet to be proven in humans.

“While the title of the paper is ‘Functional Human Liver,’ these liver buds do not contain the biliary structures (that drain toxins out of the liver) or immune cells that characterize real human liver,” added Stuart Forbes, professor of transplantation and regenerative medicine at the University of Edinburgh.

Takebe said the method may also work in such organs as the pancreas, kidneys or lungs, but that it would be another 10 years before trials are conducted on humans.